Abstract
Autosomal recessive spinocerebellar ataxia 13 (SCAR13) is a neurological disease characterized by psychomotor delay, mild to profound intellectual disability with poor or absent language, nystagmus, stance ataxia, and, if walking is acquired, gait ataxia. Epilepsy and polyneuropathy have also been documented in some patients. Cerebellar atrophy and/or ventriculomegaly may be present on brain MRI. SCAR13 is caused by pathogenic variants in the GRM1 gene encoding the metabotropic receptor of glutamate type 1 (mGlur1), which is highly expressed in Purkinje cerebellar cells, where it plays a fundamental role in cerebellar development. Here we discuss the case of an 8-year-old patient who presented with a severe neurodevelopmental disorder with balance disturbance, absence of independent walking, absence of language, diffuse hypotonia, mild nystagmus, and mild dysphagia. Whole-exome sequencing revealed a compound heterozygosity for two likely pathogenic variants in the GRM1 gene, responsible for the patient’s phenotype, and made it possible to diagnose autosomal recessive spinocerebellar ataxia SCAR13. The detected (novel) variants appear to be causative of a particularly severe picture with regard to neurodevelopment, in the context of the typical neurological signs of spinocerebellar ataxia.
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The data used for this paper will be made available by the corresponding author upon reasonable request.
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Acknowledgements
This work has been generated within the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA) (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). The authors also wish to thank the patient’s family members for their cooperation in providing the medical data for this publication.
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Conceptualization, C.A.C., G.P.; clinical data collection and data curation, C.A.C., G.P., G.T., G.S., M.G., C.S., S.R., C.F.; writing—original draft preparation, C.A.C., G.P.; writing—review and editing, C.A.C., G.P., G.T., C.S., C.F., C.D., G.S., S.G.C., L.G.; supervision, L.G., C.F. All authors have read and agreed to the published version of the manuscript.
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Cesaroni, C.A., Pisanò, G., Trimarchi, G. et al. Severe Neurodevelopmental Disorder in Autosomal Recessive Spinocerebellar Ataxia 13 (SCAR13) Caused by Two Novel Frameshift Variants in GRM1. Cerebellum (2023). https://doi.org/10.1007/s12311-023-01617-2
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DOI: https://doi.org/10.1007/s12311-023-01617-2